SSADH
MCID: SCC001
MIFTS: 56

Succinic Semialdehyde Dehydrogenase Deficiency (SSADH) malady

Neuronal diseases, Metabolic diseases categories

Summaries for Succinic Semialdehyde Dehydrogenase Deficiency

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8Disease Ontology, 21Genetics Home Reference, 42NIH Rare Diseases, 63Wikipedia, 46OMIM, 19GeneReviews, 32MalaCards
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Genetics Home Reference:21 Succinic semialdehyde dehydrogenase deficiency is a disorder that can cause a variety of neurological problems. People with this condition typically have developmental delay, especially involving speech development; intellectual disability; and decreased muscle tone (hypotonia) soon after birth. About half of those affected experience seizures, difficulty coordinating movements (ataxia), decreased reflexes (hyporeflexia), and behavioral problems. The most common behavioral problems associated with this condition are sleep disturbances, hyperactivity, difficulty maintaining attention, and anxiety. Less frequently, affected individuals may have increased aggression, hallucinations, obsessive-compulsive disorder (OCD), and self-injurious behavior, including biting and head banging. People with this condition can also have problems controlling eye movements. Less common features of succinic semialdehyde dehydrogenase deficiency include uncontrollable movements of the limbs (choreoathetosis), involuntary tensing of the muscles (dystonia), muscle twitches (myoclonus), and a progressive worsening of ataxia.

MalaCards: Succinic Semialdehyde Dehydrogenase Deficiency, also known as 4-hydroxybutyric aciduria, is related to canavan disease and wagr syndrome, and has symptoms including organic acid metabolism anomalies, psychic/behavioural troubles and hypotonia. An important gene associated with Succinic Semialdehyde Dehydrogenase Deficiency is ALDH5A1 (aldehyde dehydrogenase 5 family, member A1), and among its related pathways are Valproic Acid Pathway, Pharmacodynamics and GABA synthesis, release, reuptake and degradation. The compounds L-Aspartic Acid and carboxylate have been mentioned in the context of this disorder. Affiliated tissues include eye, globus pallidus and brain.

Disease Ontology:8 A gamma-amino butyric acid metabolism disorder that is characterized by a deficiency of succinic semialdehyde dehydrogenase resulting in elevated levels of gamma-hydroxybutyric acid.

NIH Rare Diseases:42 Succinic semialdehyde dehydrogenase (ssadh) deficiency is disorder that can cause a variety of neurological and neuromuscular problems. the signs and symptoms can be extremely variable among affected individuals and may include mild to severe intellectual disability; developmental delay (especially involving speech); hypotonia; difficulty coordinating movements (ataxia); and/or seizures. some affected individuals may also have decreased reflexes (hyporeflexia); nystagmus; hyperactivity; and/or behavioral problems. ssadh deficiency is caused by mutations in the aldh5a1 gene and is inherited in an autosomal recessive manner. management is generally symptomatic and typically focuses on treating seizures and neurobehavioral issues. last updated: 9/25/2013

Wikipedia:63 Succinic semialdehyde dehydrogenase deficiency (SSADHD), also known as 4-hydroxybutyric aciduria or... more...

Description from OMIM:46 271980

GeneReviews summary for ssadh

Aliases & Classifications for Succinic Semialdehyde Dehydrogenase Deficiency

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8Disease Ontology, 9diseasecard, 19GeneReviews, 42NIH Rare Diseases, 21Genetics Home Reference, 46OMIM, 10DISEASES, 48Orphanet, 60UMLS, 20GeneTests, 57SNOMED-CT via Orphanet, 26ICD10 via Orphanet
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Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Metabolic diseases
Anatomical: Neuronal diseases


Characteristics (Orphanet epidemiological data):

48
succinic semialdehyde dehydrogenase deficiency:
Inheritance: Autosomal recessive; Age of onset: Childhood


Aliases & Descriptions:

succinic semialdehyde dehydrogenase deficiency 8 9 19 42 21 46 10 48 60
4-hydroxybutyric aciduria 8 19 42 21 48
gamma-hydroxybutyric aciduria 8 19 21
ssadh deficiency 19 42 21
succinic semialdehyde dehydrogenase 9 20
gamma-hydroxybutyric acidemia 21
gamma-hydroxybutyricaciduria 42
4-hydroxybutyricaciduria 21
gaba metabolic defect 42
ssadh 8


External Ids:

Disease Ontology8 DOID:0060175
SNOMED-CT via Orphanet57 49748000
OMIM46 271980
ICD10 via Orphanet26 E72.8

Related Diseases for Succinic Semialdehyde Dehydrogenase Deficiency

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17GeneCards, 18GeneDecks
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Diseases related to Succinic Semialdehyde Dehydrogenase Deficiency via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show all 19)
idRelated DiseaseScoreTop Affiliating Genes
1canavan disease30.5ASPA
2wagr syndrome30.5WT1
3juvenile absence epilepsy10.4
4neuroleptic malignant syndrome10.4
5intellectual disability10.4
6obesity10.4
7sleep disorder10.4
8status epilepticus10.3
9idiopathic generalized epilepsy10.3
10d-2-hydroxyglutaric aciduria10.3
11williams syndrome10.3
12cerebritis10.0
13homocarnosinosis10.0ALDH5A1, ABAT
14pancreatitis10.0ALDH9A1
15mental retardation10.0WT1, ASPA, ALDH5A1
16epilepsy syndrome10.0ABAT, GLUD1, ALDH5A1, ASPA
17liver cirrhosis10.0ALDH9A1, GPT
18alcoholic liver cirrhosis10.0GPT, ALDH9A1
19metabolic syndrome x10.0GLUD1, ALDH9A1, ALDH5A1

Graphical network of diseases related to Succinic Semialdehyde Dehydrogenase Deficiency:



Diseases related to succinic semialdehyde dehydrogenase deficiency

Clinical Features for Succinic Semialdehyde Dehydrogenase Deficiency

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46OMIM, 48Orphanet
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Clinical features from OMIM:

271980

Clinical synopsis from OMIM:

271980

Symptoms:

48 (show all 7)
  • organic acid metabolism anomalies
  • psychic/behavioural troubles
  • hypotonia
  • ataxia/incoordination/trouble of the equilibrium
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • seizures/epilepsy/absences/spasms/status epilepticus
  • autosomal recessive inheritance

Drugs & Therapeutics for Succinic Semialdehyde Dehydrogenase Deficiency

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5CenterWatch, 41NIH Clinical Center, 6ClinicalTrials
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Approved drugs:

Search CenterWatch for Succinic Semialdehyde Dehydrogenase Deficiency

Drug clinical trials:

Search ClinicalTrials for Succinic Semialdehyde Dehydrogenase Deficiency

Search NIH Clinical Center for Succinic Semialdehyde Dehydrogenase Deficiency

Search CenterWatch for Succinic Semialdehyde Dehydrogenase Deficiency

Genetic Tests for Succinic Semialdehyde Dehydrogenase Deficiency

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20GeneTests
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Genetic tests related to Succinic Semialdehyde Dehydrogenase Deficiency:

id Genetic test Affiliating Genes
1 Succinic Semialdehyde Dehydrogenase Deficiency20 ALDH5A1

Anatomical Context for Succinic Semialdehyde Dehydrogenase Deficiency

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32MalaCards
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MalaCards organs/tissues related to Succinic Semialdehyde Dehydrogenase Deficiency:

32
Eye, Globus pallidus, Brain, Liver

Animal Models for Succinic Semialdehyde Dehydrogenase Deficiency or affiliated genes

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Publications for Succinic Semialdehyde Dehydrogenase Deficiency

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50PubMed
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Articles related to Succinic Semialdehyde Dehydrogenase Deficiency:

(show top 50)    (show all 74)
idTitleAuthorsYear
1
Thirty years beyond discovery--clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. (22739941)
2013
2
Succinic semialdehyde dehydrogenase deficiency: an inheritable neurometabolic disease]. (23516105)
2013
3
Efficacy of vigabatrin intervention in a mild phenotypic expression of succinic semialdehyde dehydrogenase deficiency. (23430864)
2012
4
Epilepsy in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. (21664777)
2011
5
Neuropathology in succinic semialdehyde dehydrogenase deficiency. (20304328)
2010
6
Cerebellar atrophy in human and murine succinic semialdehyde dehydrogenase deficiency. (20445195)
2010
7
Head bobbing due to succinic semialdehyde dehydrogenase deficiency. (20548048)
2010
8
Succinic semialdehyde dehydrogenase deficiency: decrease in 4-OH-butyric acid levels with low doses of vigabatrin]. (20018576)
2010
9
Decreased GABA-A binding on FMZ-PET in succinic semialdehyde dehydrogenase deficiency. (19667317)
2009
10
Comparative genomics of aldehyde dehydrogenase 5a1 (succinate semialdehyde dehydrogenase) and accumulation of gamma-hydroxybutyrate associated with its deficiency. (19164088)
2009
11
Circadian distribution of generalized tonic-clonic seizures associated with murine succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. (18514581)
2008
12
'Succinic semialdehyde dehydrogenase deficiency: phenotype evolution in an adolescent patient at 20-year follow-up'. (18811705)
2008
13
Neuropsychiatric morbidity in adolescent and adult succinic semialdehyde dehydrogenase deficiency patients. (18622364)
2008
14
Vigabatrin improves paroxysmal dystonia in succinic semialdehyde dehydrogenase deficiency. (17438226)
2007
15
Therapeutic concepts in succinate semialdehyde dehydrogenase (SSADH; ALDH5a1) deficiency (gamma-hydroxybutyric aciduria). Hypotheses evolved from 25 years of patient evaluation, studies in Aldh5a1-/- mice and characterization of gamma-hydroxybutyric acid pharmacology. (17457693)
2007
16
Enzymatic and metabolic evidence for a region specific mitochondrial dysfunction in brains of murine succinic semialdehyde dehydrogenase deficiency (Aldh5a1-/- mice). (17303287)
2007
17
Increased guanidino species in murine and human succinate semialdehyde dehydrogenase (SSADH) deficiency. (16504488)
2006
18
Status epilepticus in mice deficient for succinate semialdehyde dehydrogenase: GABAA receptor-mediated mechanisms. (16240371)
2006
19
Succinic semialdehyde dehydrogenase deficiency: clinical, biochemical and molecular characterization of a new patient with severe phenotype and a novel mutation. (16542398)
2006
20
Succinic semialdehyde dehydrogenase deficiency: GABAB receptor-mediated function. (16647690)
2006
21
Murine succinate semialdehyde dehydrogenase (SSADH) deficiency, a heritable disorder of GABA metabolism with epileptic phenotype. (16203683)
2005
22
Absence seizures in succinic semialdehyde dehydrogenase deficient mice: a model of juvenile absence epilepsy. (15582027)
2004
23
Liver-directed adenoviral gene transfer in murine succinate semialdehyde dehydrogenase deficiency. (15093183)
2004
24
Proton MR spectroscopy in succinic semialdehyde dehydrogenase deficiency. (15037717)
2004
25
The molecular basis of succinic semialdehyde dehydrogenase deficiency in one family. (15059623)
2004
26
Succinic semialdehyde dehydrogenase deficiency (SSADH) (4-hydroxybutyric aciduria, gamma-hydroxybutyric aciduria). (15341910)
2004
27
Mental retardation and hypotonia seen in the knock out mouse for Canavan disease is not due to succinate semialdehyde dehydrogenase deficiency. (15016427)
2004
28
Clinical spectrum of succinic semialdehyde dehydrogenase deficiency. (12743223)
2003
29
Vigabatrin and newer interventions in succinic semialdehyde dehydrogenase deficiency. (12891656)
2003
30
Succinic semialdehyde dehydrogenase deficiency in children and adults. (12891657)
2003
31
Mutational spectrum of the succinate semialdehyde dehydrogenase (ALDH5A1) gene and functional analysis of 27 novel disease-causing mutations in patients with SSADH deficiency. (14635103)
2003
32
Significant behavioral disturbances in succinic semialdehyde dehydrogenase (SSADH) deficiency (gamma-hydroxybutyric aciduria). (14512218)
2003
33
Neuroleptic malignant syndrome in a patient with succinic semialdehyde dehydrogenase deficiency. (11819156)
2002
34
A unique mouse model for succinic semialdehyde dehydrogenase deficiency with implications for gamma hydroxybutyrate intoxication. (11990378)
2002
35
Mutation analysis in a patient with succinic semialdehyde dehydrogenase deficiency: a compound heterozygote with 103-121del and 1460T>A of the ALDH5A1 gene. (11901270)
2002
36
Pharmacologic rescue of lethal seizures in mice deficient in succinate semialdehyde dehydrogenase. (11544478)
2001
37
Prenatal diagnosis of succinic semialdehyde dehydrogenase deficiency: increased accuracy employing DNA, enzyme, and metabolite analyses. (11243727)
2001
38
MRI findings in succinic semialdehyde dehydrogenase deficiency. (10774997)
2000
39
Succinic semialdehyde dehydrogenase deficiency in siblings: clinical heterogeneity and response to early treatment. (10234622)
1999
40
4-Hydroxybutyric acid and the clinical phenotype of succinic semialdehyde dehydrogenase deficiency, an inborn error of GABA metabolism. (9553943)
1998
41
Unusual enzyme findings in five patients with metabolic profiles suggestive of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria). (9686370)
1998
42
Succinic semialdehyde dehydrogenase deficiency: low excretion of metabolites in a neonate. (9061565)
1997
43
Differing clinical presentation of succinic semialdehyde dehydrogenase deficiency in adolescent siblings from Lifu Island, New Caledonia. (9266358)
1997
44
Prenatal detection of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria) (8464836)
1993
45
Succinic Semialdehyde Dehydrogenase Deficiency (20301374)
1993
46
Succinic semialdehyde dehydrogenase deficiency associated with combined 4-hydroxybutyric and dicarboxylic acidurias: potential for clinical misdiagnosis based on urinary organic acid profiling. (2926573)
1989
47
Vigabatrin therapy in patient with succinic semialdehyde dehydrogenase deficiency. (2572834)
1989
48
Urinary organic acids in succinic semialdehyde dehydrogenase deficiency: evidence of alpha-oxidation of 4-hydroxybutyric acid, interaction of succinic semialdehyde with pyruvate dehydrogenase and possible secondary inhibition of mitochondrial beta-oxidation. (3126356)
1987
49
Succinic semialdehyde dehydrogenase deficiency--a further case. (2433500)
1985
50
Succinic semialdehyde dehydrogenase deficiency: an inborn error of gamma-aminobutyric acid metabolism. (6627675)
1983

Genetic Variations for Succinic Semialdehyde Dehydrogenase Deficiency

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62UniProtKB/Swiss-Prot
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Genetic disease variations for Succinic Semialdehyde Dehydrogenase Deficiency:

62 (show all 12)
id Symbol AA change Variation ID SNP ID
1ALDH5A1p.Cys93PheVAR_026199
2ALDH5A1p.Gly176ArgVAR_026200
3ALDH5A1p.Cys223TyrVAR_026201
4ALDH5A1p.Thr233MetVAR_026202
5ALDH5A1p.Asn255SerVAR_026203
6ALDH5A1p.Gly268GluVAR_026204
7ALDH5A1p.Asn335LysVAR_026205
8ALDH5A1p.Pro382LeuVAR_026206
9ALDH5A1p.Pro382GlnVAR_026207
10ALDH5A1p.Gly409AspVAR_026208
11ALDH5A1p.Val487GluVAR_026209
12ALDH5A1p.Gly533ArgVAR_026210

Expression for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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1BioGPS, 15Gene Expression Omnibus DataSets
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Expression patterns in normal tissues for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

Search GEO for disease gene expression data for Succinic Semialdehyde Dehydrogenase Deficiency.

Pathways for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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49PharmGKB, 53Reactome, 12EMD Millipore, 29KEGG, 37NCBI BioSystems Database
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Pathways related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards/GeneDecks:

(show all 16)
idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.9ALDH5A1, ABAT
2
Hide members
9.9ALDH5A1, ABAT
39.7ALDH9A1, ABAT
4
Hide members
9.6ALDH9A1, ALDH6A1
5
Hide members
9.5ABAT, ALDH6A1, ALDH5A1
69.4GLUD1, GPT
79.3ASPA, ABAT, GPT
8
Hide members
9.1ALDH1B1, ALDH9A1
99.1ALDH9A1, ALDH1B1
10
Tyrosine metabolism p.1 (dopamine)
Hide members
9.1ALDH9A1, ALDH1B1
118.8ASPA, ALDH1B1, ALDH9A1
128.5ALDH9A1, ALDH6A1, ALDH1B1, ABAT
13
Hide members
8.2ALDH9A1, ALDH1B1, ALDH4A1, GLUD1
148.1ALDH5A1, ALDH4A1, ASPA, ABAT, GPT, GLUD1
158.0GLUD1, GPT, ALDH4A1, ALDH6A1, ALDH9A1
16
Hide members
7.0GPT, ABAT, ALDH4A1, ALDH1B1, ALDH6A1, ALDH9A1

Compounds for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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11DrugBank, 24HMDB, 44Novoseek, 28IUPHAR, 59Tocris Bioscience, 49PharmGKB, 2BitterDB
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Compounds related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards/GeneDecks:

(show all 46)
idCompoundScoreTop Affiliating Genes
1L-Aspartic Acid11 2411.0ASPA, GLUD1
2carboxylate4410.0ABAT, ASPA
3succinic semialdehyde4410.0ALDH5A1, ABAT, AKR7A2
4vigabatrin44 28 1111.9GLUD1, ABAT, ALDH5A1
5aminooxyacetic acid44 2810.9GPT, ABAT
6taurine44 59 2411.9ABAT, WT1
7succinate449.9ALDH5A1, ABAT, GLUD1
8phenelzine44 1110.9GPT, ABAT
9monoethylglycinexylidide449.8GLUD1, GPT
10l-alanine28 59 11 2412.8GPT, ABAT
11nadp+449.7GLUD1, ALDH9A1
125-hydroxytryptophol449.7ALDH9A1, GPT
13thymol44 2810.7ALDH9A1, GPT
14trichloroethylene449.6ALDH9A1, GPT
15ornithine44 2410.6ABAT, GLUD1, WT1
16valproic acid44 49 11 2412.6ALDH5A1, ABAT, GPT
17nad+449.6GLUD1, ALDH9A1, ALDH5A1
18glutaraldehyde449.6GLUD1, ALDH9A1
19aldose449.6ALDH9A1, AKR7A2
20vitamin b6449.6ALDH5A1, ABAT
21gamma-hydroxybutyrate449.6AKR7A2, GLUD1, ABAT, ALDH5A1
22Nicotinamide-Adenine-Dinucleotide119.5ALDH9A1, GLUD1
23valproate449.5GLUD1, GPT, ABAT
24pyridoxal 5-phosphate449.5GLUD1, GPT, ABAT
25gsts449.5AKR7A2, ALDH9A1
26perillic acid44 2410.5ALDH9A1, ALDH1B1
27methylmalonic acid44 2410.4ALDH1B1, ALDH9A1
285-hydroxyindoleacetic acid44 2410.4ALDH9A1, ALDH1B1
29gaba449.4GLUD1, ABAT, ALDH9A1, ALDH5A1
30alpha-ketoglutarate449.3ALDH5A1, ABAT, GPT, GLUD1
31acetyl-coa44 2410.3ALDH9A1, ALDH6A1, ASPA, GLUD1
32beta-alanine44 59 11 2412.2ALDH9A1, ALDH1B1, ABAT
33acetic acid44 28 11 2412.2ASPA, ALDH1B1, ALDH9A1
34choline44 11 2411.2ALDH9A1, GPT, GLUD1
35pyruvate449.1ALDH9A1, GPT, GLUD1
36famotidine44 2 11 2412.0ALDH4A1, ABAT, GPT, GLUD1
37l-glutamic acid28 11 2411.0GLUD1, GPT, ABAT, ALDH4A1
38(S)-Methylmalonic acid semialdehyde248.9ALDH9A1, ALDH6A1, ALDH1B1, ABAT
39glutamine448.8ALDH5A1, ABAT, GPT, GLUD1, WT1
40aspartate448.7GLUD1, GPT, ABAT, ASPA, ALDH9A1
41alanine448.7GLUD1, GPT, ABAT, ALDH9A1, ALDH5A1
42ethanol44 49 11 2411.6ALDH9A1, ALDH1B1, ABAT, GPT
43nadph44 249.3GLUD1, ABAT, ALDH4A1, ALDH1B1, ALDH9A1
44nad28 249.0GLUD1, ALDH4A1, ALDH1B1, ALDH6A1, ALDH9A1, ALDH5A1
45nadh44 11 2410.0GLUD1, ALDH4A1, ALDH1B1, ALDH6A1, ALDH9A1, ALDH5A1
46glutamate448.0GLUD1, GPT, ABAT, ASPA, ALDH4A1, ALDH9A1

GO Terms for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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16Gene Ontology
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Cellular components related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1mitochondrionGO:0057397.8ABAT, ALDH1B1, ALDH6A1, ALDH9A1, ALDH5A1, GLUD1
2mitochondrial matrixGO:0057597.5ALDH5A1, ALDH6A1, ALDH1B1, ALDH4A1, ABAT, GLUD1

Biological processes related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards/GeneDecks:

(show all 7)
idNameGO IDScoreTop Affiliating Genes
1gamma-aminobutyric acid catabolic processGO:00945010.0ABAT, ALDH5A1
2neurotransmitter catabolic processGO:04213510.0ALDH5A1, ABAT
3glutamine metabolic processGO:0065419.7ALDH5A1, GLUD1
4cellular aldehyde metabolic processGO:0060819.6AKR7A2, ALDH9A1
5cellular amino acid biosynthetic processGO:0086529.1GPT, GLUD1
6cellular nitrogen compound metabolic processGO:0346418.2ALDH9A1, ALDH6A1, ALDH4A1, GPT, GLUD1
7small molecule metabolic processGO:0442818.0GPT, ALDH4A1, ALDH6A1, ALDH9A1, GLUD1

Molecular functions related to Succinic Semialdehyde Dehydrogenase Deficiency according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1aldehyde dehydrogenase (NAD) activityGO:0040298.6ALDH9A1, ALDH1B1, ALDH4A1

Products for genes affiliated with Succinic Semialdehyde Dehydrogenase Deficiency

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  • Antibodies
  • Proteins
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Sources for Succinic Semialdehyde Dehydrogenase Deficiency

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
50PubMed
51QIAGEN
57SNOMED-CT via Orphanet
60UMLS
61UMLS via Orphanet